Up to a third of middle-aged people living with HIV infection (PLWH) experience falls each year. Falls are the most common cause of non-fatal injury in the US and the cost from emergency department visits and hospitalizations are enormous. PLWH are more susceptible to falls and their serious consequences because 1) despite control of HIV viremia, inflammation persists and underlies HIV-associated comorbidities and complications that occur at a relatively young age (so-called premature aging), 2) specific comorbidities (e.g. neuropathy, osteoporosis) and complications (e.g. frailty and impaired physical function) make falls more likely and recovery from them more difficult, 3) alcohol use exacerbates inflammation, and may increase risk for comorbidities and complications, and 4) alcohol use, illicit drug use and polypharmacy can increase the likelihood of a fall. Despite this, fall prevention has not been extensively studied among PLWH. We need interventions to address falls in PLWH but none have been tailored for this population. Understanding risk factors and targets for intervention among PLWH are essential; cohort studies can provide the information needed for intervention development. This proposal is part the Consortia for HIV/AIDS and Alcohol-Related Research Trials (CHAART). It describes the continuation and expansion of a cohort that is one of three in the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH). The URBAN ARCH theme is to address consequences of alcohol use on HIV-associated comorbidities and complications to increase treatment availability and improve outcomes. In line with that theme we propose to continue to follow and expand (to 400) an existing cohort of PLWH and a high prevalence of exposure to alcohol, illicit drugs, and polypharmacy (the Boston ARCH Cohort) in the Frailty, Functional impairment, Falls, and Fractures (4F study) to: (in 2 Primary Aims) 1) Test the associations between alcohol (and illicit drugs and polypharmacy) and falls (fractures secondarily); and 2) Test the associations between alcohol (and illicit drugs and polypharmacy) and acute healthcare utilization (emergency department use and hospitalization for falls and fractures). We will also examine the role frailty plays in these associations between alcohol, drugs and medications and the aforementioned clinical and utilization outcomes. In Exploratory Aims we will test associations between alcohol use and inflammatory markers, and between markers and HIV-associated complication outcomes (4Fs); and develop and pilot test the feasibility of a falls prevention intervention tailored to address the identified risk factors (e.g. alcohol, illicit drugs, polypharmacy) in this population. By achieving these aims we will gain substantially greater understanding of these comorbidities and complications in PLWH exposed to alcohol and other psychoactive substances; this knowledge will serve to inform the development of ways to identify, prevent and manage falls, fractures, frailty and functional impairment.